Relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer

The A2 allele of CYP17 has been associated with polycystic ovarian syndrome , elevated levels of certain steroid hormones in premenopausal women, and i ncreased breast cancer risk. We prospectively assessed the association betw een the A2 allele of CYP17 and breast cancer risk in a case-control study n ested within the Nurses' Health Study cohort. We also evaluated association s between this CYP17 genotype and plasma steroid hormone levels among postm enopausal controls not using hormone replacement to assess the biological s ignificance of this genetic variant. Women with the AZ allele were not at a n increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI ( confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% C I, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among wom en without the A2 allele (A1/A1 genotype: for age at menarche greater than or equal to 13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 gen otypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among contr ols, we found women with the A2/A2 genotype to have elevated levels of estr one (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14. 4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compare d with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independe nt risk factor for breast cancer.